Exploring the Associations Between CHRNA5 and IREB2 Gene Polymorphisms and COPD in the Kazakhstan Population

<b>Background/Objectives</b>: Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disease characterized by irreversible airway obstruction. This study aims to investigate the associations between COPD and its phenotypes with polymorphic variants of the <i>IREB2</i> and <i>CHRNA5</i> genes in the Kazakhstan population. <b>Methods</b>: A case-control study was conducted involving 265 COPD patients and 267 controls. Genotyping of the <i>IREB2</i> polymorphisms <i>rs13180</i> and <i>rs2568494</i>, as well as <i>CHRNA5 rs16969968</i> polymorphism, was performed using real-time polymerase chain reactions (Real-Time PCRs). <b>Results</b>: A higher frequency of the AA genotype of the <i>IREB2 rs2568494</i> polymorphism was identified in COPD patients with moderate to very severe airflow obstruction (Chronic Obstructive Lung Disease (GOLD) stages II, III, and IV), with an odds ratio of 0.69 (95% CI = 0.23-2.10; Padj = 0.03). The <i>IREB2 rs13180</i> polymorphism was significantly more frequent or prevalent in smokers and showed a correlation with FEV₁ (forced expiratory volume in one second) (β = 7.79, SE = 2.98, <i>p</i> = 0.01) and FEV₁/ FVC (forced vital capacity) (β = 9.51, SE = 2.95, <i>p</i> = 0.002). Additionally, the CC genotype of this polymorphism was associated with clinical manifestations of COVID-19 in COPD patients (χ²= 3,95, df = 2, <i>p</i> = 0.05). <b>Conclusions</b>: Our study identified a significant association between the <i>IREB2 rs2568494</i> polymorphism and an increased risk of severe COPD. The <i>IREB2 rs13180</i> polymorphism was linked to smoking behavior, as well as key lung function indicators, suggesting its potential role in disease progression and lung damage. Furthermore, the CC genotype of the <i>IREB2 rs13180</i> polymorphism was associated with clinical manifestations of COVID-19 in COPD patients, indicating a potential impact of this genetic variant on susceptibility to viral infections in this population.